Involvement of memory T-cells in the pathophysiology of chronic lymphocytic leukemia

Abstract

The role of T-cells in the pathogenesis of chronic lymphocytic leukemia has recently gained much attention due to the importance of the constant interaction between neoplastic B-cells with microenvironment substratum and T-cells. It is believed that these interactions modulate the clinical course of the disease, mainly through the regulation of the expansion, differentiation, and survival of chronic lymphocytic leukemia B-cells. Importantly, this crosstalk may also change the number, function, and memory phenotype of normal T-cells, thereby altering the amplitude and/or efficiency of adaptive immunity in chronic lymphocytic leukemia patients. The present study presents an overview on important aspects of this immunological crosstalk, particularly on the abnormalities of chronic lymphocytic leukemia B-cells and the alterations in normal T-cells, with focus on the CD4 memory T-cell compartment that could offer survival signals to chronic lymphocytic leukemia B-cell clone(s) and contribute to the establishment and progression of the disease. The authors believe that understanding the biological consequences of the interaction between normal T- and neoplastic B-cells in chronic lymphocytic leukemia may allow for improvements in the prognostic information and therapeutic approaches for this disease.© 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. All rights reserved.

ZAP-70 expression is associated with increased CD4 central memory T cells in chronic lymphocytic leukemia: cross-sectional study

“…The interaction of neoplastic B cells with their microenvironment, particularly CD4 + T lymphocytes and with extracellular components, could regulate the expansion, differentiation, and survival of neoplastic B cells, and possibly influence the T lymphocyte gene expression, function and phenotype. 9 , 10 This study showed that ZAP-70 positive patients presented increased T CM CD4 + T cells compared to ZAP-70 negative patients and to age-matched healthy donors ( Figure 5 ).…”

“…Although CLL is basically a B cell disease, it has been proposed that its pathophysiology and evolution are significantly influenced by T cells as they participate in their expansion, differentiation and survival, which may also influence T lymphocyte function and phenotype, 9 , 10 with the accumulation of memory T cells in CLL patients. 11 , 12 However there are few data about the association between memory T cells and the prognosis of CLL, especially related to ZAP-70.…”

Underlying Ciliary Body Uveal Melanoma in a Patient with Chronic Lymphocytic Leukemia Presenting for Hyphema

“…This unfortunate event exemplifies the profound immunosuppression associated with T cell disfunction caused by CLL. Clonal B cells in CLL uniquely interact with T cells in organized structures termed pseudofollicular proliferative centers (PC) [ 49 ] which are a hallmark of CLL and are not found in other B-cell neoplasms [ 49 ], resulting in weak stimulation leading to the generation and accumulation of CD4 central memory cells (TCM) [ 49 ]. Despite frequently elevated absolute numbers of circulating T cells [ 50 ], CLL clonal B-cells induce T cell anergy and improper Th2 polarization [ 4 ].…”

“…Despite frequently elevated absolute numbers of circulating T cells [ 50 ], CLL clonal B-cells induce T cell anergy and improper Th2 polarization [ 4 ]. CLL patients present abnormal CD4 and CD8 T-cell phenotypes [ 50 , 51 ], with the increased frequency of T cells with the senescent phenotype [ 49 ], significant shortening of T cell telomeres [ 50 ] and an inversion of the CD4:CD8 ratio [ 52 ]. Furthermore, increases in specific T-cell subsets (CD8+ and CD4*PD-1 + HLA-DR+) versus healthy subjects is associated with CLL disease progression [ 52 ].…”

Exceptional Association of Syringotropic Mycosis Fungoides with Chronic Lymphocytic Leukaemia

“…A further aspect is the role of T cells in the pathogenesis of chronic lymphocytic leukaemia. Data in the literature (12) suggest that the crosstalk between CLL B cells, extracellular components of the microenvironment, and T cells has an important impact on the physiopathology and evolution of the disease, mainly through regulation of CLL B-cell expansion, differentiation, and survival. Conversely, this crosstalk may also induce qualitative and quantitative changes in normal T cells that could impact the fitness of the immune system of CLL patients.…”